Brucellosis is a debilitating disease that can cause abortions and weight loss in animals, "undulating" fevers, "night sweats", incapacitation and arthritis in humans. It is very hardy to environmental factors, easily aerosolized and infectious through skin abrasions, ingestion and the pulmonary route. It is difficult to treat with antibiotics and often persists as a life-long infection. Brucellosis is a disease endemic to most countries, especially under-developed nations where it infects 0.1 to 10% of the livestock (e.g. cattle, swine, sheep, goats, dogs and poultry), wild life (e.g. bison, caribou, wolves, dolphins) and people.
Currently, there are no vaccines for human use to protect against brucellosis. In the past researchers have vaccinated people at high risk (e.g. veterinarians, abattoir workers) with an attenuated vaccine strain, B. abortus S19, but this appears to be attenuated for cattle and can be pathogenic or cause brucellosis in humans. There was a French vaccine (PI, or phenol insoluble) that removed the toxic lipopolysaccharide (LPS) component with phenol, but the phenol insoluble residue gave a high rate of reactogenicity (at least 53%) and led to hyper-sensitivity (vaccinates exposed to Brucella antigens were susceptible to anaphylactic shock). This latter vaccine has been discontinued and hence there are no human vaccines for brucellosis presently available.
The vaccines presently used for livestock also have their inadequacies. The one used for cattle, an attenuated B. abortus S19 vaccine strain, does not give absolute protection from disease and is about 80% protective, occasionally reverts to a pathogenic form that can cause abortions, the vaccinates cause confusion in serological tests (i.e. in some cases the positive serology can be caused by vaccination, infection, or vaccination and subsequent infection), it is virulent for animals other than cattle and it can be pathogenic for people.
In the development of a vaccine against brucellosis, the view of the scientific community was exceptionally discouraging. Below are the key points they raised:
1) Brucella was recognized over 100 years ago and for over a century researchers around the world have tried to raise a vaccine against brucellosis without success. Given the time, number of investigators and talent involved, the evidence was obvious that a vaccine could not be developed. PA1 2) Brucella was a facultative parasite that could sequester inside tissues. Not only was it protected from antibiotics and vaccine-induced antibodies of humoral immunity, but it also had mechanisms for controlling its host phagocyte (i.e. it secretes thymidine and cyclic GMP which inactivate the host cell) and hence cellular immunity is ineffective. PA1 3) Polysaccharides and bacterial glucans are very poor immunogens. The evidence is that these are the least likely candidates for vaccines.